Advancements in research on lactate dehydrogenase A in urinary system tumors.

Tumors of the urinary system, such as prostate cancer, bladder cancer, and renal cell carcinoma, are among the most prevalent types of tumors. They often remain asymptomatic in their early stages, with some patients experiencing recurrence or metastasis post-surgery, leading to disease progression. Lactate dehydrogenase A (LDHA) plays a crucial role in the glycolysis pathway and is closely associated with anaerobic glycolysis in urinary system tumors. Therefore, a comprehensive investigation into the intricate mechanism of LDHA in these tumors can establish a theoretical foundation for early diagnosis and advanced treatment. This review consolidates the current research and applications of LDHA in urinary system tumors, with the aim of providing researchers with a distinct perspective.

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery.

BACKGROUND: Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI. METHODS: In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge. RESULTS: Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p <  0.001). CONCLUSIONS: When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.

In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury?

Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized 13C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury.

Sex Differences in Renal Proximal Tubular Cell Homeostasis.

Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase-α Additionally, we quantified urinary excretion of blood plasma proteins α1-microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase-α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1-microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ-derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

Renal Function and Urinary Biomarkers in Cardiac Bypass Surgery: A Prospective Randomized Trial Comparing Three Surgical Techniques.

Background Cardiopulmonary bypass procedure is associated with an increased risk of renal impairment. To which extent structural damage causes functional decline is unknown. We evaluated perioperative kidney injury and function in patients treated with conventional extracorporeal circulation (CECC), minimized extracorporeal circulation (MECC), and off-pump coronary artery bypass grafting (OPCAB). Methods Blood and urine samples, collected at baseline and up to 72 hours after surgery from patients of the HEPCON trial (DRKS00007580, 120 patients randomized for heparin management and for surgical technique), were analyzed for differences in renal injury and function. Neutrophil gelatinase-associated lipocalin, α glutathione S-transferase, liver fatty acid-binding protein, and kidney injury molecule-1 were measured as urinary protein markers of renal tubular injury. Serum creatinine, blood urea levels, and estimated glomerular filtration rate were determined to monitor renal function. Results Markers of tubular injury differed significantly between surgical technique groups early after surgery, indicating the most detrimental effect in CECC. Hemolysis and hemodilution correlated with these early changes. A late rise did not show intergroup differences. Time courses of renal function parameters, as well as the development of acute kidney injury in 15 patients (13.5%), were irrespective of surgical technique. Heparin management did not influence renal parameters. Conclusion During coronary artery bypass grafting, CECC temporarily induces more tubular injury than MECC or OPCAB. However, late changes of renal function parameters occur irrespective of extracorporeal perfusion mode and even in off-pump surgery.

[THE ANALYSIS OF INDICATORS OF MINERAL METABOLISM IN PATIENTS WITH DEGENERATIVE DYSTROPHIC AFFECTIONS OF JOINTS].

The analysis of indicators of mineral metabolism in patients with degenerative dystrophic affections of joints demonstrated that under development of osteoarthrosis process the alteration of indicators of concentration of electrolytes in blood serum, urine and synovial fluid occurs. The stage II of process is characterized by maximal alterations of indicators. The indicator of relationship between concentration of phosphate-ion and index of phosphatases of blood serum turned out the significant coefficient of correlation.

Increased renal expression and urinary excretion of TLR4 in acute kidney injury associated with cirrhosis.

BACKGROUND: Patients with cirrhosis frequently develop renal dysfunction, a proportion of who do not fulfill criteria for hepatorenal syndrome (HRS). We hypothesized that the kidneys in these patients would exhibit histological and biomarker evidence of kidney injury. We looked specifically for TLR expression as they may mediate kidney injury. METHODS: Sixty seven subjects (6); alcoholic cirrhosis: compensated (9), acute deterioration of alcoholic cirrhosis (52)] were included. Renal dysfunction was defined as a creatinine of >133 µmol/L and/or according to the AKI network criteria. Urinary biomarkers, KIM-1, πGST, αGST and a novel biomarker, urinary TLR4 were measured. Renal biopsies were also available from eight other alcoholic cirrhosis patients (three non-HRS renal dysfunction; five HRS) that were stained for TLR4 and caspase-3. RESULTS: Fourteen patients developed renal dysfunction, amongst these three had type 2 HRS. KIM-1, πGST and αGST were higher in patients with acute deterioration of cirrhosis compared with patients with compensated cirrhosis, but did not differ between those with and without renal dysfunction. Urinary TLR4 was significantly higher in patients with renal dysfunction associated with infection/inflammation. Kidney biopsies from non-HRS renal dysfunction patients showed tubular damage with evidence of increased tubular expression of TLR4, and caspase-3. Minor changes were observed in HRS patients. CONCLUSIONS: The data provide proof of concept that renal dysfunction in patients with cirrhosis with superimposed inflammation is associated with significant tubular injury and apoptosis and with increased renal expression and urinary excretion of the TLR4, suggesting a potential role of TLR4 as mediator of renal injury.

The investigation of specific biochemical markers in monitoring kidney function of drug addicts.

INTRODUCTION: An increasingly important issue in the Polish population is drug abuse. It leads to extensive damage of parenchymal organs, including kidney. Establishing early markers of organ damage and their monitoring during rehabilitation therapy is therefore of pivotal importance. This study evaluated the utility of highly specific and selective markers (NGAL, IL-18, a and π-GST isoenzyme, and ß2-M). The influence of opioid drugs and other factors on kidney function (HIV and HCV infections, duration and the kind of drugs abused) was determined. MATERIALS AND METHODS: Urine collected from 83 subjects who abused drugs and 33 healthy volunteers was tested with ELISA using specific antibodies (IBL, Biotron, Bioporto-Diagnostics). HIV infection was confirmed with western-blotting and HCV with PCR. CD4 lymphocytes were quantified with flow cytometry. RFLP and PCR were used to determine the viral load of HIV and HCV (genotype). RESULTS: A significant increase of IL-18, NGAL and ß2M activity in heroin addicts compared to the control group was noted as well as the influence of HIV infection on NGAL and ß2M excretion. A statistically significant (p=0.04) correlation between the viral load and IL-18 concentration was noted while no significant influence of the duration and the kind of drugs abused, the route of intake or the age of addicts was seen. Only the NGAL concentration was sex dependent and significantly higher in women. DISCUSSION: This study showed the specific, clinical utility of IL-18, NGAL, and ß2M in the evaluation of renal function in drug addicts. Early detection of nephropathy with biochemical indicators might help prevent severe conditions that require hospitalization and intensive care.

[Acute pancreatitis is unknown etiology in a 15 years old teenager].

The article describes a case of acute pancreatitis in progressing course, of unspecified etiology of a 15 year old child with a lethal outcome. It is stated 6.5 times increased amylase blood and 13.5 times increased diastase of urine.

Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat; correlation of minimal histopathological changes with biomarkers of renal injury.

Hexachloro-1:3-butadiene (HCBD) causes damage specifically to the renal proximal tubule in rats. In the present study, injury to the nephron of male Hanover Wistar rats was characterized at 24 h following dosing with HCBD in the range 5-90 mg kg⁻¹ to determine the most sensitive biomarkers of damage, that is, the biomarkers demonstrating significant changes at the lowest dose of HCBD, using a range of measurements in serum and urine, renal histopathology, and renal and hepatic gene expression. Histologically, kidney degeneration was noted at doses as low as 10 mg kg⁻¹ HCBD. Significant changes in the hepatic and renal gene expression categories of xenobiotic metabolism and oxidative stress were observed at 5 mg kg⁻¹ HCBD, and in the kidney alone, evidence of inflammation at 90 mg kg⁻¹ HCBD. Increases in the urinary excretion of α-glutathione S-transferase (α-GST) and kidney injury molecule-1 (KIM-1) were seen at 10 mg kg⁻¹ HCBD, and increases in urinary excretion of albumin and total protein were evident at 15 mg kg⁻¹ HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal toxicity in Hanover Wistar rats were urinary α-GST and KIM-1. Urinary albumin measurement is also recommended as, although it is not the most sensitive biomarker, together with α-GST, albumin showed the largest relative increase of all the biomarkers investigated, and the protein is easily measured.

Urinary collagen IV and πGST: potential biomarkers for detecting localized kidney injury in diabetes--a pilot study.

BACKGROUND/AIMS: Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST). METHODS: Clinical data from 457 unselected patients attending a hospital diabetes clinic were collected. Spot urine samples were analysed for albumin and creatinine. Biomarkers were measured by enzyme-linked immunosorbent assay, and corrected to urinary creatinine. RESULTS: All 3 biomarkers correlated weakly with albumin/creatinine ratios (Pearson correlation <0.2, p values <0.001). The most common abnormality was elevated urinary collagen IV (glomerular, 35%) compared to αGST (proximal tubule, 18%) or πGST (distal tubule, 15%). The proportion of patients with abnormal biomarker results increased across the normo-, micro- and macroalbuminuria groups, with collagen IV (26, 58, 65%) and πGST (11, 25, 35%) but not αGST. CONCLUSION: In patients with diabetes, these urinary biomarkers appear to identify renal damage that is related to, but distinct from, urine albumin/creatinine ratios. The markers of glomerular fibrosis and distal tubular damage related most closely to the degree of albuminuria. Longitudinal studies are now required to assess whether these biomarkers can detect early renal disease with greater specificity and sensitivity than the albumin/creatinine ratio.

Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity.

As a result of the widespread use of Cd in industry and its extensive dissemination in the environment, there has been considerable interest in the identification of early biomarkers of Cd-induced kidney injury. Kim-1 is a transmembrane glycoprotein that is not detectable in normal kidney, but is up-regulated and shed into the urine following ischemic or nephrotoxic injury. Recent studies utilizing a sub-chronic model of Cd exposure in the rat have shown that Kim-1 is an early urinary marker of Cd-induced kidney injury. Kim-1 was detected in the urine 4-5 weeks before the onset of proteinuria and 1-3 weeks before the appearance of urinary metallothionein and Clara cell protein 16, which are standard markers of Cd nephrotoxicity. In the present study, we have compared the time course for the appearance of Kim-1 in the urine with the time course for the appearance of alpha glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucose amidase (NAG) and Cd, each of which have been used or proposed as urinary markers of Cd nephrotoxicity. Adult male Sprague-Dawley rats were given daily subcutaneous injections of 0.6 mg (5.36 micromoles)/kg Cd, 5 days per week for up to 12 weeks. One day each week, 24 h urine samples were collected and analyzed for protein, creatinine and the various markers. The results showed that significant levels of Kim-1 appeared in the urine as early as 6 weeks into the treatment protocol and then continued to rise for the remainder of the 12 week treatment period. By contrast, significant levels of alpha-GST and NAG did not appear in the urine until 8 and 12 weeks, respectively, while proteinuria was not evident until 10 weeks. The urinary excretion of Cd was below the level of detection until week 4 and then showed a slow, linear increase over the next 6 weeks before increasing markedly between weeks 10 and 12. These results provide additional evidence that Kim-1 is a sensitive biomarker of the early stages of Cd-induced proximal tubule injury.

Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury.

Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 micromol) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase (alpha-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, alpha-GST and LDH were not increased until 8-12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule.

[Urinary N-acetyl-beta-D-glucosaminidase and its isoenzymes in smoking and non-smoking workers at copper foundry occupational co-exposed to arsenic cadmium and lead]. / Aktywnosc N-acetylo-beta-D-glukozaminidazy i jej izoform w moczu palacych i niepalacych pracowników huty narazonych zawodowo na arsen, kadm i olów.

The kidneys are the critical organs in the case of a long-term occupational or environmental exposure to heavy metals and tobacco smoke. In diagnostics of renal damage useful are the methods which determine the activity of renal enzymes, quantify in urine (e.g. beta-glucuronidase, N-acetyl-beta-D-glucosaminidase). N-acetyl-beta-D-glucosaminidase (NAG) is one of the most often determined factors of tubular damage, since its activity increases in early stages of renal injury, ahead of appearance of excretory dysfunction. The aim of this research was to assess the influence of occupational exposure of copper-foundry workers to heavy metals (arsenic, cadmium, lead) on total activity of N-acetyl-beta-D-glucosaminidase and its molecular forms in urine. The investigated group was made up of 95 founders (smokers n = 51, non-smokers n = 44) and 43 people in control group (smokers n = 16, non-smokers n = 27). The concentrations of arsenic (As) and cadmium (Cd) were determined in urine, whilst the level of lead (Pb) was determined in whole blood. The activities of NAG and its isoforms were determined in urine. Smoking and non-smoking founders' urine demonstrated 14 times higher concentrations of arsenic levels in comparison with smoking and nonsmoking control group. Cadmium concentrations were 3.5 times higher in urine of smoking founders in comparison with smoking control group and about 3 times higher in case of nonsmoking founders in comparison with non-smoking control group. 7 times increase of lead concentration was observed in the whole blood within the smoking founders group in comparison with the smoking control group. In the blood of non-smoking founders was demonstrated about 10 times increase of lead concentration in comparison with the non-smoking control group. About 3-times increase of total NAG's activity was observed in urine of smoking founders and 4-times increase of non-smoking founders in comparison with smoking and non-smoking control group. The highest activity of NAG-B was observed in urine of smoking founders (11.35 +/- 7.85 U/g creatinine), then non-smoking founders (9.7 +/- 8.75 U/ g creatinine). It was confirmed, that the activity of N-acetyl-beta-D-glucosaminidase is a good factor in the assessment of occupational exposure to heavy metals like arsenic, cadmium and lead.

Pediatric reference data on activity of urinary N-acetyl-ß-D-hexosaminidase and its isoenzymes.

PURPOSE: The objective of the study was to establish age - dependent values of the urinary lysosomal exoglycosidases activities: N-acetyl-ß-D-hexosaminidase (HEX) and its isoenzyme A (HEX A) as well as isoenzyme B (HEX B) in healthy children and adolescents. MATERIAL AND METHODS: The study was performed using a random sample of 203 healthy children and adolescents (girls=99, boys=104), aged six months to 17.9 years. The activities of HEX, HEX A and HEX B were determined by a colorimetric method. The activities of the urinary HEX and its isoenzymes were expressed in pKat/µg of creatinine (pKat/µg Cr). RESULTS: Median concentrations of urinary HEX, and its HEX A, HEX B isoenzymes in particular age groups were analyzed using ANOVA. Urinary HEX, HEX A and HEX B activities (pKat/µg Cr) were the highest in children below 3 years, in comparison to remaining age groups. There were statistically significant negative correlations between urinary HEX, HEX A as well as HEX B and age (r=-0.24, p<0.001 (HEX); r=-0.20, p<0.01 (HEX A); r=-0.26, p<0.001 (HEX B), respectively. We constructed the reference values for urinary activity of HEX, HEX A and HEX B (pKat/µg Cr) in centiles according to age, in three-year intervals. CONCLUSIONS: Reported data present, for the first time, reference values for urinary activities of HEX and its isoenzymes HEX A and HEX B in children and adolescent.

Simultaneous study of the metabolic turnover and renal excretion of salivary amylase- 125 I and pancreatic amylase- 131 I in the baboon.

The metabolic turnover of salivary and pancreatic amylase was studied in the baboon, an animal with a serum amylase level and renal clearance of amylase similar to man. Purified amylase was electrolytically iodinated. Although iodinated and uniodinated amylase had similar gel filtration, electrophoretic, enzymatic, glycogen precipitation characteristics, the labeled enzyme was cleared less rapidly by the kidney than was the unlabeled material. However, urinary iodinated amylase which had been biologically screened by the kidney had a renal clearance and serum disappearance rate indistinguishable from unlabeled amylase and thus can serve as a tracer in metabolic turnover studies. Administration of a mixture of salivary amylase-(125)I and pancreatic amylase-(131)I made it possible to simultaneously measure the serum disappearance and renal clearance of these two isoenzymes. The metabolic clearance of both isoenzymes was extremely rapid with half-times of about 130 min. This rapid turnover of serum amylase probably accounts for the transient nature of serum amylase elevation which frequently occurs in pancreatitis. Pancreatic amylase-(131)I was consistently cleared more rapidly (mean clearance ratio: 1.8) by the kidney than was salivary amylase-(125)I. This more rapid renal clearance of pancreatic amylase may help to explain the disproportionate elevation of urinary amylase relative to serum amylase observed in pancreatitis.

Collagenase 2/matrix metalloproteinase 8 in critically ill patients with secondary peritonitis.

Secondary peritonitis is an important indication for surgical intensive care admissions, and it is associated with high morbidity and mortality. Collagenase 2/matrix metalloproteinase (MMP) 8 is a tissue matrix-degrading enzyme that is released from leukocytes upon inflammatory stimuli and may thus contribute to peritonitis-associated organ damage. We studied the levels and activity of MMP-8 in the peritoneal fluid of 15 critically ill patients with secondary peritonitis. The MMP-8 levels were measured from the patients' peritoneal fluid, serum, and urine, and from the serum and urine of 10 healthy controls by immunofluorometric assay. Median MMP-8 level in peritoneal fluid supernatant was 1,317 microg/L (interquartile range [IQR]) (1,254-1,359 microg/L) being significantly higher than in the sera of the patients (P=0.008). Molecular forms and isoform distribution of MMP-8, MMP-1, and MMP-13 in peritoneal fluid, assessed by Western immunoblotting, revealed that the neutrophil-type MMP-8 was the major collagenase species in peritoneal fluid, and it was partially in an activated form. Catalytically competent, active MMP-8 produced the characteristic cleavage products from intact human type I collagen. The serum levels of MMP-8 were higher in the patients, 49 microg/L (IQR, 23-214 microg/L), than in the controls, 11 microg/L (IQR, 8-24 microg/L) (P<0.01). The MMP-8 levels in the urine were higher in the patients, 0.27 microg/L (IQR, 0.04-1.89 microg/L), than in the controls, 0.03 microg/L (IQR, 0.0-0.05 microg/L) (P=0.013). Our data demonstrate for the first time that MMP-8 levels are remarkably elevated and in an active and catalytically competent form in the peritoneal fluid samples of patients with secondary peritonitis.

Renal tubular dysfunction in schizophrenic patients treated with antipsychotic drugs.

Several factors have been considered in relation to the free radical formation in schizophrenia, such as the disease itself, drug treatment and smoking. Several chemicals and drugs may cause damage to the renal tubules by different subcellular mechanisms including oxidative stress, and the aim of our study was the investigation of tubular dysfunction in schizophrenic patients. The urinary excretion of beta-N-acetylhexosaminidase (Hex) and its isoenzymes Hex A and Hex B, alpha1-microglobulin, albumin, total proteins and fractionated porphyrins were determined in 45 schizophrenic patients treated with first- and second-generation antipsychotics. In 7 patients, an increase in proteinuria of tubular origin was found, and in one as a result of mixed glomerular/tubular origin. The group of patients had a significantly higher level of excretion than the control group (n = 54) of total Hex (p < 0.001), Hex A (p < 0.05), Hex B (p < 0.001) and the relative proportion of this isoenzyme (p < 0.001). In some cases with normal levels of total Hex and urinary alpha1-microglobulin, the proportion of Hex B was already increased. Significant correlations were found for total Hex and its isoenzymes with alpha1-microglobulin (p < 0.001). Also, the porphyrins had significant correlations with total Hex (p < 0.001), Hex A (p < 0.05), Hex B (p < 0.005) and alpha1-microglobulin (p < 0.001). In the group of patients studied, it was possible to reveal early tubular cell damage (affected structural integrity) with increased excretion of Hex B, possibly mediated by free radicals, previous to the decrease in tubular reabsorption of proteins with low molecular mass filtered by the glomerulus (affected functional integrity).

Carbonic anhydorase isoenzyme I (CA-I) concentration in feces and urine as a temporary marker of occult blood in beagle dogs.

This study was undertaken to investigate whether the concentration of carbonic anhydorase isoenzyme I (CA-I) in canine feces and urine is useful as a temporary marker of occult blood. Concentrations of CA-I were measured by enzyme-linked immunosorbent assay (ELISA). Fecal CA-I concentrations in 113 healthy beagle dogs (50 male and 63 female) of various ages ranged from 4.3 to 16.7 ng/g feces (mean; 7.0 +/- 2.9 ng/g feces). One milliliter of blood from 3 healthy beagle dogs was found to contain 1,047, 1,062 and 1,150 microg CA-I. The fecal CA-I concentrations of dogs receiving intragastric infusions of autologous blood (10 ml) were very low. However, the fecal CA-I concentrations of dogs receiving infusion of autologous blood (5 ml) into the ascending colon were very high. Detection of fecal CA-I would be useful for identifying dogs with hemorrhaging of the large intestine. Of 55 urinary samples collected from healthy beagle dogs by catheter, chemical tests for occult blood were negative in 44, but CA-I concentrations ranged from 1.8 to 12.6 ng/ml (mean; 6.9 +/- 5.4 ng/ml) by ELISA. The CA-I concentrations of the other 11 samples, which tested positive for occult blood on chemical testing, ranged from 41.2 to 525.0 ng/ml by ELISA. Although CA-I is not a specific marker of erythrocytes, CA-I may be used to detect occult blood in canine feces and urine until a specific immunological test kit using antibody for Hb is developed.

Biochemical markers of acute pancreatitis.

Serum amylase remains the most commonly used biochemical marker for the diagnosis of acute pancreatitis, but its sensitivity can be reduced by late presentation, hypertriglyceridaemia, and chronic alcoholism. Urinary trypsinogen-2 is convenient, of comparable diagnostic accuracy, and provides greater (99%) negative predictive value. Early prediction of the severity of acute pancreatitis can be made by well validated scoring systems at 48 hours, but the novel serum markers procalcitonin and interleukin 6 allow earlier prediction (12 to 24 hours after admission). Serum alanine transaminase >150 IU/l and jaundice suggest a gallstone aetiology, requiring endoscopic retrograde cholangiopancreatography. For obscure aetiologies, serum calcium and triglycerides should be measured. Genetic polymorphisms may play an important role in "idiopathic" acute recurrent pancreatitis.